Table 1.

Summary of current and recent clinical trials of new diabetic kidney disease therapies

Study	Intervention	Inclusion Criteria	Main Kidney Outcomes	Main Cardiovascular Outcomes	Primary Outcome
EMPA-REG OUTCOME (NCT01131676) (45) (7)	Empagliflozin versus placebo	Type 2 diabetes History of atherosclerotic CV disease eGFR ≥30 ml/min per 1.73 m2	46% RR reduction of composite of doubling of serum creatinine accompanied by eGFR ≤45 ml/min per 1.73 m2, KRT, or death from kidney cause	38% RR reduction in CV death; 35% RR reduction of hospitalization for HF 32% RR reduction for death from any cause; no difference in nonfatal stroke or MI	CV
CANVAS (NCG01032629; NCT01989754) (46)	Canagliflozin versus placebo	Type 2 diabetes with high CV risk eGFR	40% RR reduction of kidney composite of sustained ≥40% decline in eGFR, KRT, or death from kidney causes	14% RR reduction in CV death, nonfatal MI or nonfatal stroke; 33% RR reduction for hospitalization for HF (increased amputation risk)	CV
DECLARE-TIMI-58 (NCT01730534) (47)	Dapagliflozin versus placebo	Type 2 diabetes, high CV risk eGFR >60 ml/min per 1.73 m2	47% RR reduction in kidney composite sustained ≥40% reduction in eGFR to <60 ml/min per 1.73 m2, kidney failure, kidney death	27% RR reduction in hospitalization for HF; 17% RR reduction in CV death or hospitalization for HF	CV
VERTIS CV (NCT01986881) (48)	Ertugliflozin versus placebo	Type 2 diabetes, Atherosclerotic CV disease eGFR ≥30 ml/min per 1.73 m2	19% RR reduction (nonsignificant) kidney composite (kidney death, KRT, or doubling serum creatinine) 34% RR reduction (significant) for sustained ≥40% reduction in eGFR, kidney failure, kidney death	8% RR reduction in CV death; 12% RR reduction in CV death or hospitalization for HF; no difference in MACE (CV death, nonfatal stroke or nonfatal MI)	CV
CREDENCE (NCT02065791) (15)	Canagliflozin versus placebo	Type 2 diabetes eGFR 30–90 ml/min per 1.73 m2 UACR 300–5000 mg/g Stabilized on max tolerated dose of ACEi or ARB	30% RR in kidney failure, sustained doubling of serum creatinine, kidney or CV death 28% RR reduction in secondary end point of dialysis, kidney transplant or kidney death	20% RR reduction in CV death, nonfatal stroke or MI 39% RR reduction in hospitalization for HF	Kidney and CV
DAPA-CKD (NCT03036150) (20)	Dapagliflozin versus placebo	Type 2 diabetes with diabetic kidney disease or nondiabetic kidney disease eGFR 25–75 ml/min per 1.73 m2 UACR 200–5000 mg/g Max tolerated ACEi or ARB	39% RR reduction in composite of sustained decline of eGFR >50%, kidney failure, or death from kidney or CV causes	29% RR reduction in CV death or hospitalization for HF	Kidney and CV
EMPA-KIDNEY (NCT03594110)	Empagliflozin versus placebo	Nondiabetic, eGFR between 20–45 ml/min ml/min per 1.73 m2 or CKD-EPI GFR 45–90 with UACR > 200 mg/g	Ongoing trial, primary composite end point kidney failure, sustained drop in eGFR ≥40% from baseline, kidney death or CV death	Ongoing Secondary outcome for CV death or hospitalization for HF	Kidney and CV
EMPEROR-reduced (NCT03057977) (7)	Empagliflozin versus placebo	HFrEF (Class II - IV, EF <40% and elevated BNP), eGFR > 20 ml/min with or without diabetes	Reduction in decline of eGFR from 2.28 ml/min (placebo) to 0.55 ml/min in treatment group 50% RR reduction in composite end point of KRT, sustained eGFR decline >50%	25% RR reduction in CV death or hospitalization for HF; 30% RR reduction in hospitalization for HF	HF/CV
FIDELIO-DKD (NCT02540993) (30)	Finerenonea versus placebo	Type 2 diabetes Albuminuria CKD Serum potassium less than or equal to 4.8 mmol/L	Time to first occurrence of the composite end point of onset of kidney failure, sustained decrease of eGFR ≥40% from baseline over at least 4 weeks or kidney death	14% RR reduction in CV death, nonfatal stroke, nonfatal MI, or hospitalization for HF	Kidney
SONAR (NCT01858532) (33)	ET1 blockera versus placebo On top of standard of care	Type 2 diabetes eGFR 25–75 ml/min per 1.73 m2 (cap of 300 for subjects with baseline eGFR >60 ml/min per 1.73 m2), UACR 300–5000 mg/g	35% RR reduction time to doubling of serum creatinine (confirmed by a 30-day serum creatinine) or kidney failure (<15 ml/min per 1.73 m2, dialysis or transplant)	No significant differences between CV death or hospitalization for HF	Kidney
FLOW (NCT03819153)	Semaglutide versus placebo	Type 2 diabetes eGFR 50–75 with UACR 300–5000 mg/g or eGFR 25–50 ml/min per 1.73 m2 (CKD-EPI) and UACR >100 and <5000 mg/g (on RAASa)	Ongoing trial; time to persistent eGFR decline of > or = 50%, reaching kidney failure, death from kidney disease or CV disease	Ongoing trial; CV death (primary); MACE (secondary)	Kidney and CV

EMPA-REG OUTCOME, (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; CV, cardiovascular; RR, relative risk; HF, heart failure; MI, myocardial infarction; CANVAS, CANagliflozin cardioVascular Assessment Study; DECLARE-TIMI-58, Dapagliflozin Effect on CardiovascuLAR Events; VERTIS CV, eValuation of ERTugliflozin effIcacy and Safety Cardiovascular Outcomes Trial; MACE, major adverse cardiac events; CREDENCE, Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy; UACR, urine albumin-to-creatinine ratio; ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin II type 1 receptor blockers; DAPA-CKD, Dapagliflozin in Patients with Chronic Kidney Disease; EMPA-KIDNEY, Study of Heart and Kidney Protection With Empagliflozin; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; EMPEROR-reduced, EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure with Reduced Ejection Fraction; HFrEF, heart failure with reduced ejection fraction; EF, ejection fraction; BNP, NT-proB-type natriuretic peptide; FIDELIO-DKD, FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease; SONAR, Study Of diabetic Nephropathy with AtRasentan; FLOW, Semaglutide renal outcomes trial; RAAS, renin-angiotensin-aldosterone system.

^aNo US Food and Drug Administration approval.